Oric Pharmaceuticals (ORIC) Status Update summary

Clinical program highlights

• Presented updated data from the ongoing global Phase 1b trial of ORIC-114/Enozertinib in non-small cell lung cancer, including both pretreated and treatment-naive patients with EGFR exon 20 and PACC mutations.

• Demonstrated highly competitive systemic and intracranial response rates, including in patients with active, untreated brain metastases.

• The preferred dose for future development is 80 mg once daily, based on optimal efficacy and safety balance.

• No significant off-target toxicities were observed, and the safety profile was manageable at the 80 mg dose.

• Next program update is planned for mid-2026, ahead of potential Phase 3 registrational trials.

Differentiation and competitive positioning

• Distinguished by strong CNS activity and lack of significant off-target toxicities, addressing a major unmet need in EGFR-mutated NSCLC.

• Demonstrated robust brain penetrance, with 100% intracranial response rate in first-line patients with measurable CNS disease.

• Systemic response rates are on par with or exceed competitor datasets, despite enrolling a higher proportion of patients with brain metastases.

• Tolerability at 80 mg is similar to or better than competitors, with lower rates of discontinuation and no significant cardiac, hepatic, or hematological toxicities.

• Efficacy is consistent across both near loop and far loop EGFR exon 20 mutations, as well as common and complex PACC mutations.

Dose optimization and safety

• Higher rates of grade 3 diarrhea and dose reductions were seen at 120 mg, leading to lower dose intensity and efficacy.

• At 80 mg, patients maintained dose intensity, resulting in higher and more durable response rates.

• Treatment-related adverse events were mostly grade 1 or 2, with diarrhea, paronychia, and stomatitis being the most common.

• Discontinuation rates at 80 mg were low (6%), and most discontinuations at 120 mg were due to progression rather than safety.

• 80 mg once daily selected as the recommended dose for potential Phase 3 development.